Systemic analysis of transcriptome in cancer and precancerous lesion of the esophagus and stomach

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To understand the detailed molecular mechanism of development and progression of esophageal and gastric cancer, we examined global gene expression profile in two types of primary gastric cancer through serial analysis of gene expression (SAGE), and compared with over 120 SAGE libraries of other normal and tumor tissues in the database. We have identified at least 8 genes/tags highly expressed in poorly differentiated type gastric cancer. Among them, regenerating gene type IV (Reg IV) was highly expressed in gastric cancer but not in cancer of the esophagus, lung, breast, and liver by RT-PCR. Strong expression was confirmed in gastric cancer cells by in situ hybridization. Introduction of Reg IV gene into gastric cancer cell line revealed that Reg IV protein was secreted into culture media and stimulated cell growth. We have also analyzed the gene expression profiles of the primary gastric cancer and its metastatic tumor from the same patient. It was identified 3 genes/tags (γCOP, p21 and unknown tag) whose expression was markedly reduced or lost in metastatic tumor. γCOP is one of the seven subunits forming COPI coat complex and mediates transport between Golgi and the endoplasmic reticulum. After laser capture microdissection to enrich target cells, obvious reduction in γCOP expression was confirmed in metastatic tumors by RT-PCR. We are studying the expression of these genes in precancerous lesions of the esophagus and stomach. Unknown tags detected in this study must be candidate novel genes for stomach carcinogenesis. We identified several tags specifically expressed in scattered (scirrhous) type gastric cancer, called SESs. Reverse SAGE and 5'RACE method will clone novel genes which may participate in development and progression of esophago-gastric cancer and serve as therapeutic targets.